The invention relates to a method for determining prostate cancer prognosis.
Prostate cancer represents the most common malignancy in men, and was estimated to result in approximately 39,000 related deaths in 1998 in the United States. Up to about 59% of prostate cancer cases present as a localized tumor, i.e., stages A and B, where the tumor is confined to the prostate. Clinical stage C, in which the tumor is clinically localized to the periprostatic area, but extends through the prostatic capsule and may involve seminal vesicles, represents about 14% to 18% of cases. The remaining 10% to 18% of cases are metastatic or clinical stage D.
In general, clinically aggressive behavior is associated with an accumulation of genetic aberrations in some solid tumors, such as colon cancer and urinary bladder cancer. Similar multiple genetic changes also may occur in prostate carcinoma. As prostatic cancer is a leading cause of death of males in the United States, the identification of patients whose tumor is destined to progress rapidly is a major goal of current research. Unfortunately, within a cohort of men with a single grade and stage of prostate cancer, there are few markers of clinical aggressiveness.
The invention is based, in part, on the discovery that assessing loss or gain of the 8p locus of chromosome 8, the centromere of chromosome 8, and the 8q24 locus provides a prognostic indicator for prostate cancer. Assessing the combined hybridization pattern of these markers provides a sensitive method for determining prostate cancer progression and prognosis, and leads to earlier treatment in certain cases.
In one aspect, the invention features a method for determining prostate cancer prognosis in a subject that includes determining a hybridization pattern of a set of chromosomal probes in a biological sample from the subject. The chromosomal probe set includes a probe to the 8p locus of chromosome 8 and a probe to the 8q24 locus of chromosome 8, and further can include a probe to the centromere of chromosome 8. The 8p locus can be defined further as 8p21-22 and the 8q24 locus can be defined further as the c-myc gene. The biological sample can be selected from the group consisting of prostate tissue resections, prostate tissue biopsies, urine, and bladder washings. Prostate tissue biopsies are particularly useful.
Prognosis of the subject is determined to be poor when the hybridization pattern indicates loss of the 8p locus, gain of chromosome 8, and additional increase of c-myc copy number relative to centromere copy number. Hybridization pattern can be determined by hybridizing the set of chromosomal probes to the biological sample and detecting the presence or absence of hybridized probe. The probes can be labeled, e.g. fluorescently labeled.
The invention also features a kit for determining cancer prognosis in a subject. The kit includes a set of chromosomal probes, which includes a probe to the 8p locus of chromosome 8 and a probe to the 8q24 locus of chromosome 8, and further can include a probe to the centromere of chromosome 8. The 8p locus can be defined further as 8p21-22 and the 8q24 locus can be defined further as the c-myc gene. The probes can be labeled, e.g. fluorescently labeled. The kit further can include instructions that indicate prognosis is determined to be poor when a hybridization pattern of the set of chromosomal probes indicates loss of the 8p locus, gain of chromosome 8, and additional increase of c-myc copy number relative to centromere copy number.
Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. Although methods and materials similar or equivalent to those described herein can be used to practice the invention, suitable methods and materials are described below. All publications, patent applications, patents, and other references mentioned herein are incorporated by reference in their entirety. In case of conflict, the present specification, including definitions, will control. In addition, the materials, methods, and examples are illustrative only and not intended to be limiting.
Other features and advantages of the invention will be apparent from the following detailed description, and from the claims.